Inhalation device and method

ABSTRACT

Inhalation device and associated method for facilitating inhalation by a patient of powder medicaments contained in a receptacle. The inhalation device has a chamber for receiving the receptacle. A ring is circumferentially coupled to an inner surface of the chamber to achieve a higher reproducible emitted dose of medicament from the receptacle. The inhalation device also includes an improved implement for puncturing the receptacle, requiring less force and experiencing fewer failures.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuatio of application Ser. No.10/771,447, filed Feb. 5, 2004, which is a divisional of applicationSer. No. 09/835,302, filed Apr. 16, 2001, the entirety of each of whichis incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to facilitating release ofpowder contained in a receptacle. More specifically, the presentinvention relates to the administration of medication by a method andapparatus for facilitating inhalation of powder medicaments.

2. Related Art

In the medical field, it is often desirable to administer various formsof medication to patients. Well known methods of introducing medicationinto the human body include the oral ingestion of capsules and tablets,intravenous injection through hypodermic needles, and numerous others.In one method, certain medications may be inhaled into a patient'srespiratory tract and lungs through the nose or mouth. Certain of thesemedications, such as bronchodilators, corticosteroids, etc., for thetreatment of asthma and other respiratory anomalies, may be aimed at therespiratory tract directly. Others are inhaled for purposes of systemictreatment, i.e. for treatment of any area of the body through absorptionfrom the respiratory tract through the lung tissue, into the deep lungs,and into the bloodstream. Each of these medications comes in a varietyof forms, including fluids, which are commonly administered as anaerosol vapor or mist, as well as solids. Inhalable solids typicallytake the form of fine, dry powders. Specialized devices, such asinhalers, are provided to assist the patient in directing these finepowder medications into the respiratory tract.

Various types of inhalers are known for the administration of dry powdermedicaments. However, each of these inhalers suffers certain drawbacks.For example, U.S. Pat. No. 5,787,881 discloses an inhaler that is usedwith encapsulated dry powder medicaments. However, use of this devicerequires numerous steps and imposes a number of inconveniences on auser. For example, the medication capsules used with the device have anaperture formed therein prior to insertion into an opening in theinhaler. Therefore, there exists a danger that an amount of medicationmay be lost prior to or during insertion into the device. Afterinsertion of the capsule, use of the device requires the additional stepthat a cover must be closed before the medication may be inhaled.

Inhalation devices configured for use with a capsule containing sometype of medicament are shown in U.S. Pat. No. 4,069,819 to Valentini etal. (“the '819 patent”) and U.S. Pat. No. 4,995,385 to Valentini et al.(“the '385 patent”). The inhalation device described in the '385 patentwas developed to overcome the drawbacks of the device described in the'819 patent. Particularly, in a large number of cases, the devicedescribed in the '819 patent experienced irregular and incompleteemptying of the capsule, thereby resulting in difficulties in properlyadministering the medicament in the capsule. The inhalation devicedescribed in the '385 patent attempts to overcome this deficiency bytapering the nebulization chamber toward the end surface that comprisesthe discharge holes. Thus, the nebulization chamber of the '385 patentis not cylindrical, but rather frusto-conical in form in an attempt toachieve regular complete emptying of the nebulization chamber. However,further improvements in the design of inhalation devices are needed toachieve a higher emitted dose. As used herein, “emitted dose” refers tothe percentage of the dose of powder medicament, contained in areceptacle in the inhalation device, that is emitted from the inhalationdevice. Moreover, improvements are needed to achieve higher emitteddoses that are consistently reproducible, i.e., with low standarddeviation. There is a particular need in the art for high, reproducibleemitted doses at low flow rates, as well as for high dosage ranges.

Another drawback of the inhalation devices described in the '819 and the'385 patents is the piercing device that is used to puncture thecapsule. Such conventional piercing devices are formed from circularstock, with the points created by pinching the stock at an angle,thereby creating a single sharp cutting edge. Drawbacks of such a designare that the point (which must puncture the capsule material) is oftenrounded, lessening its effectiveness as a piercing device. Moreover,burrs often form on the lower edge, which can stop the piercing devicefrom retracting from the capsule, thereby causing a device failure. Theholes formed by such a conventional piercing device are generally round,and do not have the appearance of being cut by a sharp edge. With such aconventional design, the capsule is often crushed, rather than puncturedor pierced. If such a conventional piercing device is used with brittlecapsule materials such as gelatin, pieces of capsule material of a sizethat can be inhaled are usually broken off from the capsule. Thus,conventional piercing devices are less than optimal, particularly forbrittle capsule material.

Thus, there is a need in the art for an improved method and apparatusfor inhalation of dry powder medicaments. What is needed is an inhalerthat provides for a higher emitted dose that is consistentlyreproducible with low standard deviation. Such a need is particularlyacute for low flow rates, and for high dosage ranges. There is a furtherneed in the art for an improved means for puncturing the capsulecontaining the medicament. The present invention, the description ofwhich is fully set forth below, solves the need in the art for suchimproved methods and apparatus.

SUMMARY OF THE INVENTION

The present invention relates to a method and apparatus for facilitatingrelease of powder from a device. In one aspect of the invention, adevice for emitting powder is provided. The device includes a firstcasing portion, and a second casing portion removably coupled to thefirst casing portion. A cylindrical chamber, defined by a straight wallof circular cross section, is coupled to the first casing portion. Thechamber has a proximal end and a distal end. A ring is circumferentiallycoupled to an inner surface of the chamber. The ring is preferablydisposed at approximately a midpoint of the chamber, or, alternatively,disposed adjacent the proximal end of the chamber. The second casingportion includes an emitter portion disposed at the proximal end of thechamber when the first and second casing portions are coupled together.The emitter portion defines at least one aperture configured to emitpowder therethrough.

In another aspect of the present invention, the device is configured asan inhalation device for administering powder. In this aspect of thepresent invention, the emitter portion is configured as an inhalationportion so that powder is dispersed in the chamber and administered to auser through the inhalation portion. The inhalation portion may beconfigured as a mouth piece for inhalation through the mouth, or as anose piece for inhalation through the nose.

In one aspect of the invention, the powder is contained in a receptaclethat is disposed in the chamber. Upon puncturing the receptacle, powderis dispersed in the chamber and emitted or inhaled from the device.

In yet another aspect of the present invention, the device of thepresent invention includes means for puncturing the receptacle. Themeans for puncturing can be configured as a staple. Such a staple ispreferably configured in a substantially U-shape, having two prongs. Inone aspect of the present invention, each of the prongs has a squarecross-section. In another aspect of the present invention, thesubstantially U-shaped staple includes a rounded portion and two prongsthat define a non-planar inner edge and a non-planar outer edge of thestaple, the staple being formed from a rectangular length having two endsurfaces and four planar side surfaces that intersect to form fournon-planar edges. The inner edge of the staple is configured to be oneof the non-planar edges, and the outer edge of the staple is thenon-planar edge that is opposite that non-planar edge. Each end surfaceis an angled diamond-shaped surface. In a preferred aspect, each endsurface has a top point at an apex of the inner edge, and a bottom pointat an apex of the outer edge, each top point forming a cutting point forone of the prongs.

In still a further aspect of the present invention, a method fordispensing powder by inhalation is provided. Such a method comprises

-   -   providing a powder inhalation device, the device comprising        -   a first casing portion,        -   a cylindrical chamber, defined by a straight wall of            circular cross-section, coupled to said first casing            portion, said chamber having a proximal end and a distal end            and configured to receive a receptacle therein, said chamber            comprising a ring circumferentially coupled to an inner            surface of said chamber, and        -   a second casing portion removably coupled to said first            casing portion, said second casing portion comprising an            inhalation portion disposed at the proximal end of said            chamber when said first and said second casing portions are            coupled, said inhalation portion comprising a hemispheric            region defining a plurality of apertures configured to emit            powder therethrough;    -   puncturing the receptacle to disperse powder in said chamber;        and    -   inhaling the powder through said inhalation portion.

In one aspect of the present invention, the inhaling step is carried outby inhaling the powder through a mouthpiece into a user's mouth.Alternatively, the inhaling step may be carried out by inhaling thepowder through a nose piece into a user's nose.

FEATURES AND ADVANTAGES

One feature of the present invention is that it provides high emitteddoses that are consistently reproducible over a range of flow rates anddosage quantity. Advantageously, the present invention improves theemitted dose at both low flow rates and high dose ranges. A particularlyadvantageous feature of the present invention is its ability to operateat low flow rates, such as would be associated with a child or a personwith a respiratory disease.

One advantage of the present invention is that the preferred means forpuncturing used in the device is less expensive to manufacture thanconventional piercing devices. Moreover, the means for puncturing of thepresent invention advantageously provides improved puncturingperformance since less force is needed to puncture the receptacles, andfewer failures result than with conventional piercing devices.

Another advantage of the preferred means for puncturing is animprovement to the flow rate independence of the inhaler. Consequently,the powdered medicament delivered to a patient will be independent ofhow fast the patient breathes, thereby ensuring that a consistent doseof medicament is delivered each time.

Another advantageous feature of the present invention is the accuracy ofmedicament dosage delivered thereby. Since only one dosage of medicationis present in the inhaler during each use, the possibility of overdoseis eliminated, and the medicament need not be metered prior to delivery.A patient may simply inhale all medicament present in the device.

Because the present invention operates only under the inhalative powerof the patient, the inhaler carries the additional advantage that noaccessory device, such as a compressed air cylinder or other propellant,needs to be used in conjunction with the present invention.

Another advantage of the present invention is that during inhalation,the medicament is subjected to mixing in the dispersion chamber. Thishelps to ensure that the medicament exiting the inhaler and entering thepatient's respiratory system is in the form of a fine dry powder,facilitating medicament deposition in the lungs. In addition, inhalationof finer powders is typically more comfortable for the patient.

Still another advantage of the present invention is that it can be usedwith individuals who cannot breathe hard, such as a child or anasthmatic, or individuals who are sleeping or in a coma.

Yet another advantage of the apparatus of the present invention is thatit is reusable. To reuse, a patient removes the emptied receptacle, andreplaces it with a fresh receptacle filled with the proper dose ofmedicament.

BRIEF DESCRIPTION OF THE FIGURES

The present invention is described with reference to the accompanyingdrawings. In the drawings, like reference numbers indicate identical orfunctionally similar elements.

FIG. 1 is a front view of one embodiment of a device of the presentinvention;

FIG. 2 is a cross-section of the device shown in FIG. 1 along line 2-2;

FIG. 3 is an enlarged partial cross-section of one embodiment of adispersion chamber of the present invention;

FIG. 4 is an enlarged partial cross-section of another embodiment of adispersion chamber of the present invention showing one location for aring in the dispersion chamber;

FIG. 5 is an enlarged partial cross-section of another embodiment of adispersion chamber of the present invention showing another location fora ring in the dispersion chamber;

FIG. 6 is an enlarged partial cross-section of another embodiment of adispersion chamber of the present invention showing another location fora ring in the dispersion chamber;

FIG. 7A is a top view of a preferred embodiment of a staple suitable foruse with the device of the present invention;

FIG. 7B is a front view of the embodiment shown in FIG. 7A;

FIG. 7C is a side view of the embodiment shown in FIG. 7A;

FIG. 7D is an isometric view of the embodiment shown in FIG. 7A;

FIG. 8 shows the puncture obtained with the staple shown in FIGS. 7Athrough 7D;

FIG. 9A shows a partial view of another embodiment of a staple suitablefor use with the device of the present invention;

FIG. 9B illustrates the puncture obtained with the staple shown in FIG.9A;

FIG. 10 is a bar graph illustrating emitted dose at flow rates of 20L/min (left bar), 40 L/min (center bar), and 60 L/min (right bar) forfour dispersion chamber configurations;

FIG. 11 is a bar graph illustrating emitted dose at low flow rates fordevices with varying numbers of slits;

FIG. 12 is a bar graph showing a comparison of mass fractiondistributions obtained for 6 mg (left bar) and 50 mg (right bar) fillweights;

FIG. 13 is a graph showing glucose levels (mg/dL) in beagle dogs afteradministration of insulin using an aerosol generator and a device of thepresent invention with the low ring configuration substantially as shownin FIG. 4;

FIG. 14 is a bar graph illustrating the percentage emitted dose as afunction of air volume; and

FIG. 15 is an exploded cross-sectional view of an alternate embodimentof a device of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Overview

The present invention provides an improved method and apparatus forfacilitating release of powder. In a preferred embodiment, the powder iscontained in a receptacle. As used herein, the term “receptacle”includes but is not limited to, for example, a capsule, blister, filmcovered container well, chamber, and other suitable means of storing apowder known to those skilled in the art. The present invention will bedescribed below in the context of a method and apparatus for dispensingdry powder medicaments for inhalation by a patient. However, it shouldbe apparent to one skilled in the art that the invention is not limitedto such an exemplary embodiment, and could be used for other purposes.

As will be described in more detail below, an apparatus of the presentinvention is an inhaler that includes a chamber. In one embodiment, thechamber is configured to receive the receptacle containing themedicament. To improve the emptying of the receptacle and provide ahigher reproducible emitted dose, the chamber includes a ringcircumferentially coupled to an inner surface of the chamber. The ringis preferably disposed at approximately a midpoint of the chamber, oralternatively, adjacent the proximal end of the chamber. In proper use,air will exit the inhaler carrying a full dose of medicament in the formof a fine, dry powder.

The inhaler of the present invention is preferably configured with ameans for puncturing the receptacle that improves puncturingperformance, particularly with brittle receptacle material. The meansfor puncturing the receptacle of the present invention is preferablyconfigured as a substantially U-shaped staple with two prongs, eachprong having a sharp point and two cutting edges. In one embodiment ofthe present invention, each prong has a square cross-section, with thestaple material being bent around a face so that the innermost part ofthe U-shaped staple is flat. In another embodiment of the presentinvention, the staple material is rotated 45 degrees so that it is bentaround an edge so that the innermost part of the U-shaped staple is anedge. In such an embodiment, the end surface of each prong is an angleddiamond-shaped surface.

The methods of the present invention use an inhaler to dispense powderby inhalation. As will be discussed in greater detail below, a useroperates the device to puncture the receptacle to disperse powder in thechamber, and inhales the powder through the inhalation portion.

Inhaler and Associated Method of the Present Invention

A front view of one embodiment of an inhalation device 100 of thepresent invention is shown in FIG. 1. The rear view of device 100 issubstantially identical to the front view. Device 100 includes a firstor lower casing portion 120 and a second or upper casing portion 130removably coupled to first casing portion 120. Upper casing portion 130and lower casing portion 120 include a flattened region 132 and 122,respectively, for ease of gripping the casing for use by a patient.Lower casing portion 120 preferably includes an outer casing 126 and aninner casing 124 movably received within outer casing 126. A removablecap 110 is provided at the user or inhalation end of the device.

Preferred materials for device 100 include Food and Drug Administration(FDA) approved, USP tested plastics. Preferably, device 100 ismanufactured using an injection molding process, the details of whichwould be readily apparent to one skilled in the art.

FIG. 2 is a cross-section of device 100 shown in FIG. 1 along line 2-2.As shown in FIG. 2, device 100 includes an inhalation or emitter portion220. Inhalation portion 220 comprises a hemispheric region 222 thatdefines a plurality of apertures 224. It should be understood that thepresent invention is not limited to a particular number of apertures224, and can be configured such that at least one aperture 224 isprovided. An inhalation piece 226 is provided to allow for inhalation ofthe medicament by a user. Inhalation piece 226 can be configured as amouth piece for inhalation through a user's mouth. Alternatively,inhalation piece 226 can be configured as a nose piece for inhalationthrough a user's nose.

Device 100 includes a cylindrical chamber 210 that is defined by astraight wall 212 of circular cross-section. Chamber 210 has a proximalend 214 and a distal end 216. A plurality of slits 218 are defined bywall 212, and are configured for introducing air into chamber 210 todisperse powder released from a capsule 219. It should be understoodthat the present invention is not limited to a particular number ofslits 218, and can be configured such that at least one slit 218 isprovided. Powder released from capsule 219 is dispersed in chamber 210and inhaled through apertures 224 and inhalation piece 226 by the user.

In other embodiments of the invention, receptacles other than capsulesare used, such as blisters and film covered container wells as is knownin the art. In one embodiment, the volume of the receptacle is at leastabout 0.37 cm³. In another embodiment, the volume of the receptacle isat least about 0.48 cm³. In yet another embodiment, the receptacles havea volume of at least about 0.67 cm³ or 0.95 cm³. In one embodiment ofthe invention, the receptacle is a capsule designated with a capsulesize 2, 1, 0, 00, or 000. Suitable capsules can be obtained, forexample, from Shionogi (Rockville, Md.). Blisters can be obtained, forexample, from Hueck Foils, (Wall, N.J.).

The receptacle encloses or stores particles, also referred to herein aspowders. The receptacle is filled with particles in a manner known toone skilled in the art. For example, vacuum filling or tampingtechnologies may be used. Generally, filling the receptacle with powdercan be carried out by methods known in the art. In one embodiment of theinvention, the particle or powder enclosed or stored in the receptaclehave a mass of about 5 milligrams (mg). Preferably the mass of theparticles stored or enclosed in the receptacle is at least about 10 mg.

In one embodiment of the present invention, particles used with thedevice have a tap density of less than about 0.4 g/cm³. Particles havinga tap density of less than about 0.4 g/cm³ are referred to herein as“aerodynamically light”. In a preferred embodiment, the particles have atap density of near to or less than about 0.1 g/cm³. Tap density is ameasure of the envelope mass density characterizing a particle. Theenvelope mass density of particles of a statistically isotropic shape isdefined as the mass of the particle divided by the minimum sphereenvelope volume within which it can be enclosed. Features that cancontribute to low tap density include irregular surface texture andhollow or porous structure. Particularly preferred particles and powdersare described in U.S. Pat. Nos. 6,136,295, 5,985,309, 5,874,064, and5,855,913, and U.S. patent application Ser. No. 09/591,307, filed Jun.9, 2000 entitled “High Efficient Delivery of a Large Therapeutic MassAerosol”, the entirety of each of the foregoing patents and patentapplications is hereby incorporated herein by reference.

Device 100 includes a means for puncturing 230 that is used to puncturecapsule 219 to release powder contained therein into chamber 210. In theembodiment shown in FIG. 1, means for puncturing 230 is configured as asubstantially U-shaped staple having two prongs 232. In this embodiment,each of prongs 232 is configured with a square cross-section 234,thereby providing a sharp point and two cutting edges. This will bediscussed in more detail below with respect to FIGS. 9A and 9B. Asdiscussed in more detail below, device 100 could alternatively beconfigured with the puncturing implement shown in FIGS. 7A through 7D.As can be readily appreciated by one skilled in the art, the presentinvention is not limited to use of a substantially U-shaped staple asthe means for puncturing the capsule. Alternatively, one, or a pluralityof, straight needle-like implements could be used. Preferably, thepuncturing implement is configured to puncture at least two holes in thecapsule.

Means for puncturing 230 is preferably configured to be movable betweena non-puncturing position (as depicted in FIG. 1) and a puncturingposition. In the puncturing position, prongs 232 pierce or puncturecapsule 219 to make holes therein. In a preferred embodiment, a meansfor biasing is provided that biases the means for puncturing 230 in thenon-puncturing position. In the embodiment shown in FIG. 2, the meansfor biasing is configured as a spring 242 that biases the substantiallyU-shaped staple in the non-puncturing position.

As noted with respect to FIG. 1, device 100 includes inner casing 124and outer casing 126. As shown in FIG. 2, a spring 244 is disposed inlower casing portion 120 that biases inner casing 124 in an outwardposition. Upon compression of spring 244, inner casing 124 moves fromthe outward position to an inward position, thereby drawing lower casingportion 120 toward upper casing portion 130. Compression of spring 244also causes compression of spring 242, thereby causing means forpuncturing 230 to move to the puncturing position. Upon release ofcompression, springs 242 and 244 return to their biased state, therebyreturning means for puncturing 230 to its non-puncturing position, andinner casing 124 to its outward position.

A pair of flanges 252 is disposed on first casing portion 120. A pair ofgrooves 254 is disposed on second casing portion 130 so that flanges 252can be received within grooves 254 to thereby couple the first andsecond casing portions. Preferably, the first and second casing portionsare coupled with a friction-fit engagement. A friction-fit engagementcan be achieved using the groove and flange arrangement depicted in FIG.2. Other alternative configurations for a friction-fit engagement wouldbe readily apparent to one skilled in the art.

FIG. 3 is an enlarged partial cross-section of one embodiment of chamber210. In the embodiment shown in FIG. 3, chamber 210 does not contain aring disposed on an inner surface, and an inner diameter of chamber 210is depicted as “X”. Such a configuration may be referred to herein as a“straight” chamber configuration.

FIG. 4 is an enlarged partial cross-section of another embodiment ofchamber 210. In the embodiment shown in FIG. 4, a ring 400 iscircumferentially coupled to an inner surface of chamber 210. An innerdiameter of ring 400 is depicted as “Y”, and is less than inner diameterX of chamber 210. In the embodiment shown in FIG. 4, ring 400 isdisposed at approximately a midpoint of chamber 210. Such aconfiguration may be referred to herein as a “low” ring position or“low” chamber configuration. As shown in FIG. 4, in the low ringposition, ring 400 is disposed adjacent slits 218. The ring position ismeasured by the distance from the top of hemispheric region 222 to thebottom edge of ring 400. This distance is depicted as “Z”. The followingdimensions are provided as exemplary dimensions of a device of thepresent invention. It should be understood by one skilled in the artthat the present invention is not limited to the dimensions providedherein, or to any particular dimensions. In one embodiment of thechamber 210 shown in FIG. 4, diameter X is 0.47 in., diameter Y is 0.38in., and distance Z is 0.49 in.

FIG. 6 is an enlarged partial cross-section of another embodiment ofchamber 210. In the embodiment shown in FIG. 6, ring 400 iscircumferentially coupled to an inner surface of chamber 210. An innerdiameter of ring 400 is depicted as “Y”, and is less than inner diameterX of chamber 210. In the embodiment shown in FIG. 6, ring 400 isdisposed adjacent the proximal end of chamber 210. Such a configurationmay be referred to herein as a “high” ring position or a “high” chamberconfiguration. The ring position is measured by the distance from thetop of hemispheric region 222 to the bottom edge of ring 400. Thisdistance is depicted as “Z”. The following dimensions are provided asexemplary dimensions of a device of the present invention. It should beunderstood by one skilled in the art that the present invention is notlimited to the dimensions provided herein, or to any particulardimensions. In one embodiment of the chamber 210 shown in FIG. 6,diameter X is 0.47 in., diameter Y is 0.38 in., and distance Z is 0.29in.

FIG. 5 is an enlarged partial cross-section of another embodiment ofchamber 210. In the embodiment shown in FIG. 5, ring 400 iscircumferentially coupled to an inner surface of chamber 210. An innerdiameter of ring 400 is depicted as “Y”, and is less than inner diameterX of chamber 210. In the embodiment shown in FIG. 5, ring 400 isdisposed between the low ring position of FIG. 4 and the high ringposition of FIG. 6. Such a configuration may be referred to herein as a“mid” ring position or “mid” chamber configuration. The ring position ismeasured by the distance from the top of hemispheric region 222 to thebottom edge of ring 400. This distance is depicted as “Z”. The followingdimensions are provided as exemplary dimensions of a device of thepresent invention. It should be understood by one skilled in the artthat the present invention is not limited to the dimensions providedherein, or to any particular dimensions. In one embodiment of thechamber 210 shown in FIG. 5, diameter X is 0.47 in., diameter Y is 0.38in., and distance Z is 0.39 in.

In one embodiment of the present invention, ring 400 is integral withchamber 210. In such an embodiment, ring 400 and chamber 210 are formedas a unit, such as through an injection molding, extrusion or a castingprocess. In another embodiment of the present invention, ring 400 isattached to the inner surface of chamber 210 in a manner known to thoseskilled in the art, such as through the use of glue or other type ofadhesive, or by using an attaching device such as a pin or screw, etc.Preferably, the casing of device 100 is made from a material that can beinjection molded, such as a plastic material (preferably FDA approved,USP tested). As would be readily apparent to one skilled in the art, thematerial is preferably durable, easy to clean, and non-reactive withpowder medicaments.

An exploded cross-sectional view of an alternate embodiment of a device1500 of the present invention is shown in FIG. 15. Device 1500 includesa first or lower casing portion 1540 and a second or upper casingportion 1550 removably coupled to first casing portion 1540. First andsecond casing portions 1540 and 1550 are coupled through the use of aflange 1552 and a groove 1554. Preferred materials for device 1500include Food and Drug Administration (FDA) approved, USP testedplastics. Preferably, device 1500 is manufactured using an injectionmolding process, the details of which would be readily apparent to oneskilled in the art.

Device 1500 includes an inhalation or emitter portion 1520. Inhalationportion 1520 comprises a hemispheric region 1522 that defines aplurality of apertures 1524. It should be understood that the presentinvention is not limited to a particular number of apertures 1524, andcan be configured such that at least one aperture 1524 is provided. Aninhalation piece 1526 is provided to allow for inhalation of themedicament by a user. Inhalation piece 1526 can be configured as a mouthpiece for inhalation through a user's mouth. Alternatively, inhalationpiece 1526 can be configured as a nose piece for inhalation through auser's nose.

Device 1500 includes a cylindrical chamber 1510 that is defined by astraight wall 1512 of circular cross-section. A plurality of slits 1518are defined by wall 1512, and are configured for introducing air intochamber 1510 to disperse powder released from, for example, capsule 219as illustrated in FIG. 2. It should be understood that the presentinvention is not limited to a particular number of slits 1518, and canbe configured such that at least one slit 1518 is provided. Powderreleased from capsule 219 is dispersed in chamber 1510 and inhaledthrough apertures 1524 and inhalation piece 1526 by the user.

As would be readily apparent to one skilled in the art, device 1500 canbe configured with means for puncturing and means for biasing in amanner similar to that described above with respect to the embodimentshown in FIGS. 1 and 2. Means for puncturing are described in moredetail below with respect to FIGS. 7A through 7D, 8, 9A, and 9B.Moreover, device 1500 can be configured with the chamber designsdescribed above with respect to FIGS. 3-6.

FIG. 10 is a bar graph illustrating emitted dose at flow rates of 20L/min (left bar), 40 L/min (center bar), and 60 L/min (right bar) for atotal volume of 2 L for four dispersion chamber configurations (standarddeviations shown; sample size n=3). The flow rates were measured with aflow meter. The emitted dose measurement involved placing a capsule intofour embodiments of the inhaler of the present invention for actuationinto an emitted dose (ED) measurement apparatus. The ED apparatusincluded a powder filter and a filter holder. The powder collected bythe ED apparatus was quantified by fluorescence spectrophotometry. Thestraight configuration is shown in FIG. 3; the low configuration isshown in FIG. 4; the mid configuration is shown in FIG. 5; and the highconfiguration is shown in FIG. 6. As can be seen from FIG. 10, each ofthe low, mid, and high configurations demonstrated a higher emitted doseat each of the three flow rates than the straight (no ring)configuration. Thus, the ring configuration of the present inventionprovides an improvement over conventional chamber designs without aring, such as those shown in the '819 and '385 patents. At each of theflow rates shown in FIG. 10, the low configuration produced a higheremitted dose and a lower standard deviation than the mid and highconfigurations.

FIG. 11 is a bar graph illustrating emitted dose at low flow rates fordevices with varying numbers of slits 218. A flow rate of less thanabout 15 L/min will be referred to herein as a “low flow rate.” Themeasurements were taken at a flow rate of 5 L/min, with a volume of 67cc and a 15 mg dosage. As show in FIG. 11, by decreasing the number ofslits 218, the emitted dose increases so that the device of the presentinvention successfully delivers a high emitted dose at low flow rateover multiple (ten) actuations. Thus, the device of the presentinvention achieves a high emitted dose at low flow rates that isconsistently reproducible with low standard deviation.

Experiments were conducted to evaluate the emitted dose as a function ofair volume drawn through the inhaler. The inhaler was operated at aconstant flow rate of 30 L/min for a 5 mg dose. The volume of airthrough the inhaler was varied by varying the actuation time. Volumes of0.5, 1.0, 1.5, 2.0 and 3.0 L were investigated. FIG. 14 shows thepercentage emitted dose as a function of air volume (n=3, standarddeviations shown). The emitted dose remained constant across the rangeof volumes and was consistently reproducible with low standarddeviation.

In the embodiments having the inner diameter X of chamber 210 of 0.47in. and the inner diameter Y of ring 400 of 0.38 in., the ratio of theinner diameter of the ring to the inner diameter of the chamber is about0.8. By modifying the inner diameters of the ring and the chamber, it ispossible to optimize the emitted dose at varying flow rates. As reportedin Annals of the ICRP, Human respiratory tract model for radiologicalprotection, 24 (1-3), Elsevier Science, Inc., New York, 1994, the flowrate for a tidal breathing seated adult male is 300 mL/s (18 L/min) fora volume of 750 mL. In one embodiment of a device of the presentinvention optimized for low flow rates (less than about 15 L/min), innerdiameter X of chamber 210 is 0.33 in. and inner diameter Y of ring 400is 0.30 in. In such an embodiment, the ratio of the inner diameter ofthe ring to the inner diameter of the chamber is about 0.9. Preferably,the ratio of the inner diameter of the ring to the inner diameter of thechamber is about 0.9 or less.

The device of the present invention can also be optimized for varyingdosage ranges. One way to do so is to vary the dimensions of chamber 210to accommodate varying sizes of capsules. For example, a chamber havingan inner diameter X of 0.33 in., inner diameter Y of 0.30 in., anddistance Z of 0.57 in. can be used with size 2 and size 00 capsules. Itshould be readily apparent to one skilled in the art that chamber 210can be scaled to accommodate varying capsule sizes, and to accommodatethose capsule sizes at varying flow rates.

The device of the present invention can be used with varying dosageranges. A highly dispersible powder was prepared and loaded intocapsules to obtain a large pre-metered dose (50 mg) and a smallerpre-metered dose (6 mg). The particle size characteristics of the powderwere as follows: Dg=10.6 μm; ρ=0.11 g/cc; and Da=3.5 μm, where Dg is themean geometric diameter, p is the powder density, and Da is the meanaerodynamic diameter. The aerodynamic particle size distributions werecharacterized using a multistage liquid impinger that extracted air at60 L/min after actuating the inhaler device (D). As shown in FIG. 12,the mass fraction was measured at D, the induction port (IP) of theimpactor, stages S1-S4, and the filter cutoff (SF). Size 2 capsules wereused for the 6 mg dose and size 000 capsules were used for the 50 mgdose. FIG. 12 shows the results comparing the two particle sizedistributions obtained for the 6 mg (left bar) and 50 mg (right bar)doses. “ED” used on the graph refers to emitted dose, and FPM used onthe graph refers to fine particle mass (estimate of the mass that woulddeposit in the lungs). The fine particle fraction <6.8 μm relative tothe total dose (FPF_(TD)<6.8 μm) for the 6 and 50 mg doses were 74.4%and 75.0%, respectively. Similar aerodynamic particle size distributionswere obtained for both doses.

FIG. 13 is a graph showing glucose (mg/dL) in beagle dogs afteradministration of human insulin using an aerosol generator and a deviceof the present invention with the low ring configuration substantiallyas shown in FIG. 4. The generator is a device with proven ability forforming a respirable aerosol that results in deposition of powder in doglungs. Metered powder is presented to a chamber where the powder isdispersed by a high velocity jet of air. The dispersed powder isdirected toward a baffle to separate large agglomerates beforeinhalation by the dog. The pharmakodynamic profile shown in FIG. 13confirms that the device of the present invention produces a pattern ofpowder deposition similar to the aerosol generator.

The dogs were anesthetized for the dosing procedure. A forced maneuverwas used with dogs being ventilated at 75% of their vital capacity(approximately 100 cc/s or 6 L/min for a duration of 1 second). A 4second breath-hold was applied at the end of each inhalation. Aphysically smaller device was used with the low ring configuration tofacilitate administration. The device performed well at the low flowrate with the anesthetized dogs using the forced maneuver. Based onthese results, such a device could be used with a sleeping person or aperson having breathing problems, such as from chronic obstructivepulmonary disease (COPD).

As can be seen from the description above, the device of the presentinvention relies upon the breath of the user to drive the inhalationprocess, yet the device is configured to work successfully at low flowrates. As such, the device of the present invention has particularsuitability for use with individuals who cannot breath hard, such as achild, an individual with respiratory disease, or individuals who aresleeping or in a coma.

Turning now to FIGS. 7A through 7D, a preferred embodiment of a staplesuitable for use in the present invention is shown. The staplepreferably comprises a rectangular length of material that has fourplanar side surfaces 730. Each planar side surface intersects with twoother planar side surfaces to create a total of four non-planar edges736. The staple is preferably bent into a substantially U-shapedconfiguration, thereby having a rounded portion and two prongs 732. Theprongs 732 terminate at two end surfaces 731. As best seen in FIGS. 7A,7C and 7D, end surfaces 731 are diamond-shaped.

The diamond-shaped end surfaces are created by bending the materialabout a non-planar edge. This configuration is best shown in FIGS. 7Band 7D. As can be seen, each prong 732 has an inner surface 738 thatcomprises one of the non-planar edges and an outer surface 740 thatcomprises the opposite non-planar edge. The inner surface 738 of eachprong 732 terminates at the uppermost portion 737 of the diamond-shapedend surface, thereby creating a cutting edge for the prong. The outersurface 740 of the prong 732 terminates at the lowermost portion 735 ofthe diamond-shaped end surface.

FIGS. 9A and 9B depict another embodiment of a staple suitable for usein the present invention. This staple preferably comprises a rectangularlength of material that has four planar side surfaces. Each planar sidesurface intersects with two other planar side surfaces to create a totalof four non-planar edges. The staple is preferably bent into asubstantially U-shaped configuration, thereby having a rounded portionand two prongs. The prongs terminate at two end surfaces that have asquare shape.

The square-shaped end surfaces are created by bending the material abouta planar side surface. As shown in FIG. 9A, each prong has an innersurface that comprises one of the planar side surfaces and an outersurface that comprises the opposite planar side surface. The innersurface of each prong terminates at the uppermost portion of thesquare-shaped end surface, thereby creating a cutting edge for theprong. The outer surface of the prong terminates at the lowermostportion of the square-shaped end surface.

FIG. 9B illustrates a puncture obtained from using the staple depictedin FIG. 9A. As shown, the holes formed by this staple have theappearance of being cut with a sharp edge. In addition, the materialremoved to create the hole is peeled back and remains well attached tothe capsule; thereby preventing the capsule material from being inhaledby the user when the powder medicament is being dispensed.

FIG. 8 illustrates a puncture obtained from using the staple depicted inFIGS. 7A-7D. The holes formed by the staple appear to be cut with asharp edge, and the excess material is peeled back. In testing, theeffort required to puncture the capsule is lower than circular sectionstaples, and approximately the same as a square section staple. However,during testing, no instances were noted of crushed or otherwisemispunctured capsules. These staples are extremely inexpensive toproduce, approximately one-third the cost of square section staples suchas those depicted in FIG. 9A.

In addition to improved puncturing performance, drug delivery fromcapsules punctured with the staple depicted in FIGS. 7A-7D is greatlyimproved. The Emitted Dose (ED) and Fine Particle Fraction (FPF) of atest powder was measured at both 20 and 60 Liters per minute (LPM). Inall cases, the aerosol emitted from capsules punctured with the diamondsection staple of FIGS. 7A-7D was improved over a conventional circularstock staple. Most significantly, the FPF of powder delivered at 20liters per minute was improved almost to the level of the FPF at 60liters per minute.

The present invention also relates to a method for dispensing powdermedicaments to a user through the various embodiments of the disclosedinhalation device. In such a method, a receptacle containing the powdermedicament, e.g., a capsule 219, is placed or formed into cylindricalchamber 210. When the user compresses the inhalation device, staple 230is moved toward capsule 219 thereby puncturing capsule 219 to cause therelease of powder into chamber 210. After release into the chamber, thepowder is then inhaled by the user through apertures 224 and inhalationpiece 226. As noted, inhalation piece 226, can be configured as either amouth piece or a nose piece. For subsequent uses, the user merelyreplaces emptied capsule 219 with another capsule 219 that contains anew supply of power medicament. Alternatively, powder medicament isinjected into a permanent receptacle that is formed into chamber 210.

CONCLUSION

While various embodiments of the present invention have been describedabove, it should be understood that they have been presented by way ofexample only, and not limitation. For example, the present invention isnot limited to the physical arrangements or dimensions illustrated ordescribed. Nor is the present invention limited to any particular designor materials of construction. As such, the breadth and scope of thepresent invention should not be limited to any of the above-describedexemplary embodiments, but should be defined only in accordance with thefollowing claims and their equivalents.

1. A device for emitting powder contained in a receptacle, comprising: afirst casing portion; a cylindrical chamber, defined by a straight wallof circular cross-section, coupled to said first casing portion, saidchamber having a proximal end and a distal end and configured to receivethe receptacle therein, said chamber comprising a ring circumferentiallycoupled to an inner surface of said chamber, wherein an inner diameterof said ring is less than an inner diameter of said chamber wherebyemitted dose from said powder inhalation device is improved compared toa device with no ring; and a second casing portion removably coupled tosaid first casing portion, said second casing portion comprising aninhalation portion disposed at the proximal end of said chamber whensaid first and said second casing portions are coupled, said inhalationportion comprising a hemispheric region defining a plurality ofapertures configured to emit powder therethrough.
 2. The device of claim1, further comprising: a substantially U-shaped staple comprising arounded portion and two prongs that define a non-planar inner edge and anon-planar outer edge of said staple, wherein said staple is formed froma rectangular length having two end surfaces and four planar sidesurfaces that intersect to form four non-planar edges, wherein saidinner edge of said staple is one of said non-planar edges and said outeredge is another of said non-planar edges that is opposite said onenon-planar edge, wherein each end surface is an angled diamond-shapedsurface.
 3. The device of claim 1, wherein said ring is disposed atapproximately a midpoint of said chamber.
 4. A method for efficient dosedelivery of a medicament contained in a receptacle, comprising:providing a powder inhalation device, the device comprising a firstcasing portion, a cylindrical chamber, defined by a straight wall ofcircular cross-section, coupled to said first casing portion, saidchamber having a proximal end and a distal end and configured to receivethe receptacle therein, said chamber comprising a ring circumferentiallycoupled to an inner surface of said chamber, wherein an inner diameterof said ring is less than an inner diameter of said chamber wherebyemitted dose from said powder inhalation device is improved compared toa device with no ring, and a second casing portion removably coupled tosaid first casing portion, said second casing portion comprising aninhalation portion disposed at the proximal end of said chamber whensaid first and said second casing portions are coupled, said inhalationportion comprising a hemispheric region defining a plurality ofapertures configured to emit powder therethrough. inhaling the emitteddose through said plurality of apertures at a flow rate less than about15 L/min.